Long-term follow-up of indolent lymphoma patients treated with high-dose sequential chemotherapy and autografting: Evidence that durable molecular and clinical remission frequently can be attained only in follicular subtypes

Purpose: To evaluate the prognostic relevance of molecular monitoring of minimal residual disease in indolent lymphomas receiving high-dose sequential chemotherapy and autografting. Patients, Materials, and Methods: A polymerase chain reaction-(PCR-)based strategy was used to evaluate the presence of residual tumor cells in a panel of 70 indolent lymphoma patients: 40 with follicular (FCL), 14 with small lymphocytic (SLL), and 16 with mantle-cell (MCL) lymphomas. They were treated either with first-line (n = 61) or second-line (n = 9) therapy with an intensified high-dose chemotherapy program followed by peripheral-blood progenitor cells autografting. The Bcl-1, Bcl-2, and immunoglobulin gene rearrangements were used as lymphoma-specific markers. Overall, a molecular marker was obtained from the diagnostic tissue in 60 of 70 patients (86%). Results: The collection of PCR-negative cells and the achievement of posttransplantation molecular remission (MR) were common in patients with FCL subtype (54% and 70%, respectively), whereas they were not frequent among SLL and MCL (25% and 12.5%, respectively) patients. With a median molecular follow-up of 75 months, an 88% incidence of relapse was observed among patients never attaining MR. In contrast, relapse incidence was only 8% among patients attaining a durable MR (P < .005). At present, 26 patients (20 with FCL and six with non-FCL) are long-term survivors in absence of clinical and molecular disease. Conclusion: Our results indicate that among indolent lymphomas, FCL and non-FCL subtypes show a significantly different behavior in terms of MR achievement, and MR after intensive chemotherapy and autografting is predictive for a prolonged disease-free survival, whereas persistent PCR positivity is associated with a high risk of relapse.